Microenvironmental influences on human B-cell development

F. E. Bertrand, Craig E Eckfeldt, J. R. Fink, A. S. Lysholm, J. A R Pribyl, N. Shah, Tucker W LeBien

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Mammalian B-cell development can be viewed as a developmental performance with several acts. The acts are represented by checkpoints centered around commitment to the B-lineage and functional Ig gene rearrangement - culminating in expression of the pre-B-cell receptor (pre-BCR) and the BCR. Progression of cells through these checkpoints is profoundly influenced by the fetal liver and adult bone marrow (BM) stromal cell microenvironments. Our laboratory has developed a model of human B-cell development that utilizes freshly isolated/non-transformed human BM stromal cells as an in vitro microenvironment. Human CD34+ hematopoietic stem cells plated in this human BM stromal cell microenvironment commit to the B lineage and progress through the pre-BCR and BCR checkpoints. This human BM stromal cell microenvironment also provides survival signals that prevent apoptosis in human B-lineage cells. Human B-lineage cells exhibit differential expression of Notch receptors and human BM stromal cells express the Notch ligand Jagged-1. These results suggest a potential role for Notch in regulating B-lineage commitment and/or progression through the pre-BCR and BCR checkpoints.

Original languageEnglish (US)
Pages (from-to)175-186
Number of pages12
JournalImmunological Reviews
Volume175
DOIs
StatePublished - 2000

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